i) Field of the Invention
The present invention relates to a novel thrombin-binding substance, more particularly to a thrombin-binding substance useful as a medicine especially as a remedy for thrombosis and the like owing to its effects to the anticoagulation and fibrinolytic systems which control the coagulation of blood, and to a process for its preparation.
ii) Description of the Prior Art
A great deal of work has been done regarding the role that thrombin plays as a proteolytic enzyme in the control mechanism of blood coagulation and the mechanism of the coagulation system has been elucidated for the most part.
N. L. Esmon et al. have recently reported that thrombin activates in the organism Protein C which is said to act on the fibrinolytic and anticoagulant systems. They also reported the existence of a certain substance in extracts of rabbit lung tissue functioning as a coenzyme for the activation mechanism, and named it thrombomodulin [J. Biological Chemistry, 257(2) 859-864 (1982)].
Aoki, one of the present inventors, and others also reported human thrombomodulin separated from human placenta. The substance had similar properties to those reported by N. L. Esmon et al., with a molecular weight of about 71,000 in an unreduced condition [Thromb. Res. 37, 353-364 (1985)].
Furthermore, I. Maruyama et al. reported that they compared the activities of human thrombomodulin separated from human placentae and having a molecular weight of about 75,000 with those of the above rabbit thrombomodulin and they had identical activities [J. Clin, Invest. 75, 987-991, (March 1985)].
It has also been reported recently by H. Ishii et al. that human plasma and urine contain substances having the same activities as thrombomodulin and the molecular weights of such substances in plasma are about 63,000 and 54,000 [J. Clin. Invest. 76, 2178-2181 (Dec. 1985)].